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Yorodumi- PDB-7ak6: Cryo-EM structure of ND6-P25L mutant respiratory complex I from M... -
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-Basic information
Entry | Database: PDB / ID: 7ak6 | |||||||||
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Title | Cryo-EM structure of ND6-P25L mutant respiratory complex I from Mus musculus at 3.8 A | |||||||||
Components |
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Keywords | OXIDOREDUCTASE / Complex I with mutation | |||||||||
Function / homology | Function and homology information response to injury involved in regulation of muscle adaptation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / blastocyst hatching / circulatory system development ...response to injury involved in regulation of muscle adaptation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / blastocyst hatching / circulatory system development / response to light intensity / protein insertion into mitochondrial inner membrane / respiratory system process / psychomotor behavior / Mitochondrial protein degradation / cellular response to oxygen levels / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / cardiac muscle tissue development / : / [2Fe-2S] cluster assembly / oxygen sensor activity / adult walking behavior / respiratory chain complex I / cellular response to glucocorticoid stimulus / deoxynucleoside kinase activity / negative regulation of non-canonical NF-kappaB signal transduction / positive regulation of mitochondrial membrane potential / response to hydroperoxide / cellular respiration / ubiquinone-6 biosynthetic process / iron-sulfur cluster assembly / mitochondrial ribosome / adult behavior / dopamine metabolic process / positive regulation of ATP biosynthetic process / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / apoptotic mitochondrial changes / NADH dehydrogenase activity / mitochondrial ATP synthesis coupled electron transport / : / mitochondrial electron transport, NADH to ubiquinone / : / proton motive force-driven mitochondrial ATP synthesis / mitochondrial respiratory chain complex I assembly / ubiquinone binding / acyl binding / neuron development / NADH dehydrogenase (ubiquinone) activity / cellular response to interferon-beta / acyl carrier activity / quinone binding / electron transport coupled proton transport / ATP synthesis coupled electron transport / negative regulation of reactive oxygen species biosynthetic process / cellular response to retinoic acid / negative regulation of intrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway / ATP metabolic process / : / tricarboxylic acid cycle / visual perception / aerobic respiration / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / mitochondrion organization / cerebellum development / neurogenesis / regulation of mitochondrial membrane potential / response to hormone / response to cocaine / fatty acid metabolic process / synaptic membrane / kidney development / muscle contraction / mitochondrial membrane / apoptotic signaling pathway / electron transport chain / sensory perception of sound / regulation of protein phosphorylation / ionotropic glutamate receptor binding / response to nicotine / response to hydrogen peroxide / multicellular organism growth / response to organic cyclic compound / mitochondrial intermembrane space / brain development / negative regulation of cell growth / cognition / 2 iron, 2 sulfur cluster binding / circadian rhythm / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.82 Å | |||||||||
Authors | Yin, Z. / Bridges, H.R. / Grba, D. / Hirst, J. | |||||||||
Funding support | United Kingdom, 2items
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Citation | Journal: Nat Commun / Year: 2021 Title: Structural basis for a complex I mutation that blocks pathological ROS production. Authors: Zhan Yin / Nils Burger / Duvaraka Kula-Alwar / Dunja Aksentijević / Hannah R Bridges / Hiran A Prag / Daniel N Grba / Carlo Viscomi / Andrew M James / Amin Mottahedin / Thomas Krieg / ...Authors: Zhan Yin / Nils Burger / Duvaraka Kula-Alwar / Dunja Aksentijević / Hannah R Bridges / Hiran A Prag / Daniel N Grba / Carlo Viscomi / Andrew M James / Amin Mottahedin / Thomas Krieg / Michael P Murphy / Judy Hirst / Abstract: Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease- ...Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
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PDBx/mmCIF format | 7ak6.cif.gz | 1.4 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7ak6.ent.gz | 1.2 MB | Display | PDB format |
PDBx/mmJSON format | 7ak6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ak6_validation.pdf.gz | 2.4 MB | Display | wwPDB validaton report |
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Full document | 7ak6_full_validation.pdf.gz | 2.4 MB | Display | |
Data in XML | 7ak6_validation.xml.gz | 207.3 KB | Display | |
Data in CIF | 7ak6_validation.cif.gz | 317.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ak/7ak6 ftp://data.pdbj.org/pub/pdb/validation_reports/ak/7ak6 | HTTPS FTP |
-Related structure data
Related structure data | 11811MC 7ak5C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10605 (Title: Single particle cryo-EM dataset of Mus musculus mitochondrial complex I with ND6 P25L mutation Data size: 3.1 TB Data #1: Single particle cryo-EM dataset of Mus musculus mitochondrial complex I with ND6 P25L mutation [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-NADH-ubiquinone oxidoreductase chain ... , 7 types, 7 molecules AHJKLMN
#1: Protein | Mass: 13251.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: P03899, NADH:ubiquinone reductase (H+-translocating) |
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#8: Protein | Mass: 36105.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: P03888, NADH:ubiquinone reductase (H+-translocating) |
#10: Protein | Mass: 18672.145 Da / Num. of mol.: 1 / Mutation: P25L / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: A9UIY5, UniProt: P03925*PLUS, NADH:ubiquinone reductase (H+-translocating) |
#11: Protein | Mass: 10637.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: P03903, NADH:ubiquinone reductase (H+-translocating) |
#12: Protein | Mass: 68547.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: P03921, NADH:ubiquinone reductase (H+-translocating) |
#13: Protein | Mass: 51943.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: P03911, NADH:ubiquinone reductase (H+-translocating) |
#14: Protein | Mass: 38800.230 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: P03893, NADH:ubiquinone reductase (H+-translocating) |
-NADH dehydrogenase [ubiquinone] iron-sulfur protein ... , 7 types, 7 molecules BCDIQRe
#2: Protein | Mass: 24715.912 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: Q9DC70, NADH:ubiquinone reductase (H+-translocating) |
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#3: Protein | Mass: 30191.307 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: Q9DCT2, NADH:ubiquinone reductase (H+-translocating) |
#4: Protein | Mass: 52720.602 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: Q91WD5, NADH:ubiquinone reductase (H+-translocating) |
#9: Protein | Mass: 24068.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: Q8K3J1, NADH:ubiquinone reductase (H+-translocating) |
#17: Protein | Mass: 19814.725 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CXZ1 |
#18: Protein | Mass: 13041.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: P52503 |
#30: Protein | Mass: 12675.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q99LY9 |
-NADH dehydrogenase [ubiquinone] flavoprotein ... , 3 types, 3 molecules EFs
#5: Protein | Mass: 27318.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: Q9D6J6, NADH:ubiquinone reductase (H+-translocating) |
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#6: Protein | Mass: 50904.152 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: Q91YT0, NADH:ubiquinone reductase (H+-translocating) |
#44: Protein | Mass: 11833.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q8BK30 |
-Protein , 3 types, 4 molecules GTUY
#7: Protein | Mass: 79866.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart References: UniProt: Q91VD9, NADH:ubiquinone reductase (H+-translocating) | ||
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#20: Protein | Mass: 17390.289 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CR21 #24: Protein | | Mass: 15130.416 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: G5E814 |
-NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit ... , 11 types, 11 molecules OPSVWXZabqr
#15: Protein | Mass: 40657.375 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q99LC3 |
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#16: Protein | Mass: 42588.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9DC69 |
#19: Protein | Mass: 10932.675 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQ75 |
#21: Protein | Mass: 13380.719 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CPP6 |
#22: Protein | Mass: 15311.858 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQZ5 |
#23: Protein | Mass: 20025.127 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9DCJ5 |
#25: Protein | Mass: 16881.588 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9ERS2 |
#26: Protein | Mass: 7921.279 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: O35683 |
#27: Protein | Mass: 9338.867 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQ91 |
#42: Protein | Mass: 17112.416 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q7TMF3 |
#43: Protein | Mass: 12506.432 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9Z1P6 |
-NADH dehydrogenase [ubiquinone] 1 subunit ... , 2 types, 2 molecules cd
#28: Protein | Mass: 8636.023 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQY9 |
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#29: Protein | Mass: 14185.692 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQ54 |
-NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit ... , 11 types, 11 molecules fghijklmnop
#31: Protein | Mass: 6965.109 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: P0DN34 |
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#32: Protein | Mass: 17463.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: O09111 |
#33: Protein | Mass: 21742.197 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQH3 |
#34: Protein | Mass: 15540.085 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q3UIU2 |
#35: Protein | Mass: 11982.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CPU2 |
#36: Protein | Mass: 11714.240 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQZ6 |
#37: Protein | Mass: 21903.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9D6J5 |
#38: Protein | Mass: 15105.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQC7 |
#39: Protein | Mass: 22020.123 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CQJ8 |
#40: Protein | Mass: 16360.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9CR61 |
#41: Protein | Mass: 21054.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: heart / References: UniProt: Q9DCS9 |
-Non-polymers , 10 types, 21 molecules
#45: Chemical | ChemComp-SF4 / #46: Chemical | ChemComp-PC1 / | #47: Chemical | #48: Chemical | ChemComp-FMN / | #49: Chemical | ChemComp-3PE / #50: Chemical | #51: Chemical | ChemComp-ATP / | #52: Chemical | ChemComp-NDP / | #53: Chemical | ChemComp-ZN / | #54: Chemical | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Mouse mitochondrial complex I with ND6-P25L mutation / Type: COMPLEX Details: Proline to leucine substitution at position 25 in the ND6 subunit of complex I Entity ID: #1-#44 / Source: NATURAL |
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Molecular weight | Value: 1 MDa / Experimental value: NO |
Source (natural) | Organism: Mus musculus (house mouse) / Strain: C57BL/6J / Organelle: Mitochondrion / Tissue: heart |
Buffer solution | pH: 7.14 |
Specimen | Conc.: 3.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: Quantifoil R0.6/1 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS / Details: Preliminary grid screening was performed manually. |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50.015 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
EM imaging optics | Energyfilter slit width: 20 eV |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.82 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 25629 / Symmetry type: POINT |